Diaz-Munoz, MD;
Kiselev, VY;
Le Novere, N;
Curk, T;
Ule, J;
Turner, M;
(2017)
Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells.
Nature Communications
, 8
, Article 530. 10.1038/s41467-017-00454-2.
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Abstract
Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis in a CAP-independent manner. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response.
| Type: | Article |
|---|---|
| Title: | Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-017-00454-2 |
| Publisher version: | http://doi.org/10.1038/s41467-017-00454-2 |
| Language: | English |
| Additional information: | © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CLASS SWITCH RECOMBINATION, MAMMALIAN STRESS GRANULES, MHC CLASS-I, DNA-DAMAGE, GERMINAL-CENTER, V(D)J RECOMBINATION, GENOMIC STABILITY, GENOTOXIC STRESS, ATAXIA-TELANGIECTASIA, DEFICIENT LYMPHOCYTES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1576483 |
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